University of Vienna, Center for Molecular Biology, Max F. Perutz Laboratories, Doktor-Bohr-Gasse 9, A-1030 Vienna, Austria.
Br J Cancer. 2011 Jan 18;104(2):229-34. doi: 10.1038/sj.bjc.6606009. Epub 2010 Nov 16.
The epidermis is the outermost layer of the body and protects it from environmental insults. This crucial function is sustained by a continuous process of self-renewal involving the carefully balanced proliferation and differentiation of progenitor cells constantly replacing the mature cells at the surface of the epidermis. Genetic changes in the signalling pathways controlling keratinocyte proliferation and differentiation disrupt this balance and lead to pathological changes including carcinogenesis. This review discusses the role of Ras, an oncogene critically involved in the development of skin neoplasia, and its downstream effector Raf in epidermal homeostasis and tumourigenesis. In particular, we will focus on the recently established role of Raf-1 as the decisive element that, by restraining keratinocyte differentiation, allows the development and maintenance of Ras-driven tumours.
表皮是身体的最外层，保护身体免受环境侵害。这种关键功能是通过一个连续的自我更新过程维持的，涉及祖细胞的精细平衡增殖和分化，这些祖细胞不断取代表皮表面的成熟细胞。控制角质形成细胞增殖和分化的信号通路中的遗传变化破坏了这种平衡，导致包括癌变在内的病理变化。这篇综述讨论了 Ras 的作用，Ras 是一种在皮肤肿瘤发生中至关重要的癌基因，及其下游效应物 Raf 在表皮稳态和肿瘤发生中的作用。特别是，我们将重点介绍 Raf-1 作为决定性因素的新作用，通过限制角质形成细胞分化，允许 Ras 驱动的肿瘤的发展和维持。
